Plasma and CSF oxytocin levels after intranasal and intravenous oxytocin in awake macaques

Abstract

Oxytocin (OT) is a neuropeptide that mediates a variety of complex social behaviors in animals and humans. Intranasal OT has been used as an experimental therapeutic for human conditions characterized by deficits in social functioning, especially autism spectrum disorder and schizophrenia. However, it is currently under intense debate whether intranasal delivery of OT reaches the central nervous system. In this study, four female rhesus macaques were implanted with chronic intrathecal catheters and used to investigate the pharmacokinetic profile of OT in the central nervous system and the peripheral vasculature following intravenous (IV) and intranasal (IN) administration of OT. In a randomized, crossover design, OT was given to four awake monkeys at three different doses based on body weight (0.1IU/kg; 1IU/kg; 5IU/kg). A time course of concurrent cerebrospinal fluid (CSF) and plasma samples were taken following administration. We found a dose-dependent effect of IV OT treatment on plasma OT levels, which peaked at 5min post-dose and gradually returned to baseline by 120min. In contrast, a change in CSF OT was only observed at the highest IV dose (5IU/kg) at 15min post-dose and gradually returned to baseline by 120min. After IN administration, there was no significant change in plasma OT at any of the three doses. However, at the highest dose level, we found a significant increase in CSF OT at 15–30min post- dose. The results of this study in light of recent, similar publications highlight the importance of methodological consistency across studies. This study also establishes a non-human primate model that can provide a stable platform for carrying out serial sampling from the central nervous system and peripheral vasculature concurrently.